Development and validation of a quantitative coronary CT Angiography model for diagnosis of vessel-specific coronary ischemia

Background: Noninvasive stress testing is commonly used for detection of coronary ischemia but possesses variable accuracy and may result in excessive health care costs. Objectives: This study aimed to derive and validate an artificial intelligence-guided quantitative coronary computed tomography angiography (AI-QCT) model for the diagnosis of coronary ischemia that integrates atherosclerosis and vascular morphology measures (AI-QCTISCHEMIA) and to evaluate its prognostic utility for major adverse cardiovascular events (MACE). Methods: A post hoc analysis of the CREDENCE (Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia) and PACIFIC-1 (Comparison of Coronary Computed Tomography Angiography, Single Photon Emission Computed Tomography [SPECT], Positron Emission Tomography [PET], and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve) studies was performed. In both studies, symptomatic patients with suspected stable coronary artery disease had prospectively undergone coronary computed tomography angiography (CTA), myocardial perfusion imaging (MPI), SPECT, or PET, fractional flow reserve by CT (FFRCT), and invasive coronary angiography in conjunction with invasive FFR measurements. The AI-QCTISCHEMIA model was developed in the derivation cohort of the CREDENCE study, and its diagnostic performance for coronary ischemia (FFR ≤0.80) was evaluated in the CREDENCE validation cohort and PACIFIC-1. Its prognostic value was investigated in PACIFIC-1. Results: In CREDENCE validation (n = 305, age 64.4 ± 9.8 years, 210 [69%] male), the diagnostic performance by area under the receiver-operating characteristics curve (AUC) on per-patient level was 0.80 (95% CI: 0.75-0.85) for AI-QCTISCHEMIA, 0.69 (95% CI: 0.63-0.74; P < 0.001) for FFRCT, and 0.65 (95% CI: 0.59-0.71; P < 0.001) for MPI. In PACIFIC-1 (n = 208, age 58.1 ± 8.7 years, 132 [63%] male), the AUCs were 0.85 (95% CI: 0.79-0.91) for AI-QCTISCHEMIA, 0.78 (95% CI: 0.72-0.84; P = 0.037) for FFRCT, 0.89 (95% CI: 0.84-0.93; P = 0.262) for PET, and 0.72 (95% CI: 0.67-0.78; P < 0.001) for SPECT. Adjusted for clinical risk factors and coronary CTA-determined obstructive stenosis, a positive AI-QCTISCHEMIA test was associated with an HR of 7.6 (95% CI: 1.2-47.0; P = 0.030) for MACE. Conclusions: This newly developed coronary CTA-based ischemia model using coronary atherosclerosis and vascular morphology characteristics accurately diagnoses coronary ischemia by invasive FFR and provides robust prognostic utility for MACE beyond presence of stenosis.info:eu-repo/semantics/acceptedVersio

Relationship of age, atherosclerosis and angiographic stenosis using artificial intelligence

Objective: The study evaluates the relationship of coronary stenosis, atherosclerotic plaque characteristics (APCs) and age using artificial intelligence enabled quantitative coronary computed tomographic angiography (AI-QCT). Methods: This is a post-hoc analysis of data from 303 subjects enrolled in the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial who were referred for invasive coronary angiography and subsequently underwent coronary computed tomographic angiography (CCTA). In this study, a blinded core laboratory analysing quantitative coronary angiography images classified lesions as obstructive (≥50%) or non-obstructive (\u3c50%) while AI software quantified APCs including plaque volume (PV), low-density non-calcified plaque (LD-NCP), non-calcified plaque (NCP), calcified plaque (CP), lesion length on a per-patient and per-lesion basis based on CCTA imaging. Plaque measurements were normalised for vessel volume and reported as % percent atheroma volume (%PAV) for all relevant plaque components. Data were subsequently stratified by age \u3c65 and ≥65 years. Results: The cohort was 64.4±10.2 years and 29% women. Overall, patients \u3e65 had more PV and CP than patients \u3c65. On a lesion level, patients \u3e65 had more CP than younger patients in both obstructive (29.2 mm3 vs 48.2 mm3; p\u3c0.04) and non-obstructive lesions (22.1 mm3 vs 49.4 mm3; p\u3c0.004) while younger patients had more %PAV (LD-NCP) (1.5% vs 0.7%; p\u3c0.038). Younger patients had more PV, LD-NCP, NCP and lesion lengths in obstructive compared with non-obstructive lesions. There were no differences observed between lesion types in older patients. Conclusion: AI-QCT identifies a unique APC signature that differs by age and degree of stenosis and provides a foundation for AI-guided age-based approaches to atherosclerosis identification, prevention and treatment

Diabetes, atherosclerosis, and stenosis by AI

OBJECTIVEThis study evaluates the relationship between atherosclerotic plaque characteristics (APCs) and angiographic stenosis severity in patients with and without diabetes. Whether APCs differ based on lesion severity and diabetes status is unknown.RESEARCH DESIGN AND METHODSWe retrospectively evaluated 303 subjects from the Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia (CREDENCE) trial referred for invasive coronary angiography with coronary computed tomographic angiography (CCTA) and classified lesions as obstructive (≥50% stenosed) or nonobstructive using blinded core laboratory analysis of quantitative coronary angiography. CCTA quantified APCs, including plaque volume (PV), calcified plaque (CP), noncalcified plaque (NCP), low-density NCP (LD-NCP), lesion length, positive remodeling (PR), high-risk plaque (HRP), and percentage of atheroma volume (PAV; PV normalized for vessel volume). The relationship between APCs, stenosis severity, and diabetes status was assessed.RESULTSAmong the 303 patients, 95 (31.4%) had diabetes. There were 117 lesions in the cohort with diabetes, 58.1% of which were obstructive. Patients with diabetes had greater plaque burden (P = 0.004). Patients with diabetes and nonobstructive disease had greater PV (P = 0.02), PAV (P = 0.02), NCP (P = 0.03), PAV NCP (P = 0.02), diseased vessels (P = 0.03), and maximum stenosis (P = 0.02) than patients without diabetes with nonobstructive disease. APCs were similar between patients with diabetes with nonobstructive disease and patients without diabetes with obstructive disease. Diabetes status did not affect HRP or PR. Patients with diabetes had similar APCs in obstructive and nonobstructive lesions.CONCLUSIONSPatients with diabetes and nonobstructive stenosis had an association to similar APCs as patients without diabetes who had obstructive stenosis. Among patients with nonobstructive disease, patients with diabetes had more total PV and NCP.Cardiolog

Interface engineering for high-performance direct methanol fuel cells using multiscale patterned membranes and guided metal cracked layers

Capability to fabricate high-performance membrane electrode assemblies (MEAs) is a key to the commercialization of direct methanol fuel cells (DMFCs). This work reports an interface engineering method to introduce a multiscale patterned membrane and a guided metal cracked layer between the catalyst layer and the membrane by the creep-assisted sequential imprinting and simple stretching technique. The MEA with a multiscale patterned membrane, where the nanopatterns covered the whole surface even on the side surface of microstructures, showed improved performance owing to enhanced mass transport by the thinned electrode, effective utilization of the active sites, and increased Pt utilization. To obtain further performance enhancement, we incorporated a guided gold cracked layer into the MEA with the multiscale patterned membrane. The electrochemically inactive thin gold layer acted as a physical barrier for methanol crossover and the guided cracks provided multiple proton pathways. Our interface engineering utility resulted in an enhancement of the device performance by 42.3% compared with that of the reference © 2017 Elsevier Ltd. All rights reserved1

Specific bile acids inhibit hepatic fatty acid uptake in mice

UnlabelledBile acids are known to play important roles as detergents in the absorption of hydrophobic nutrients and as signaling molecules in the regulation of metabolism. We tested the novel hypothesis that naturally occurring bile acids interfere with protein-mediated hepatic long chain free fatty acid (LCFA) uptake. To this end, stable cell lines expressing fatty acid transporters as well as primary hepatocytes from mouse and human livers were incubated with primary and secondary bile acids to determine their effects on LCFA uptake rates. We identified ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) as the two most potent inhibitors of the liver-specific fatty acid transport protein 5 (FATP5). Both UDCA and DCA were able to inhibit LCFA uptake by primary hepatocytes in a FATP5-dependent manner. Subsequently, mice were treated with these secondary bile acids in vivo to assess their ability to inhibit diet-induced hepatic triglyceride accumulation. Administration of DCA in vivo via injection or as part of a high-fat diet significantly inhibited hepatic fatty acid uptake and reduced liver triglycerides by more than 50%.ConclusionThe data demonstrate a novel role for specific bile acids, and the secondary bile acid DCA in particular, in the regulation of hepatic LCFA uptake. The results illuminate a previously unappreciated means by which specific bile acids, such as UDCA and DCA, can impact hepatic triglyceride metabolism and may lead to novel approaches to combat obesity-associated fatty liver disease

Ultra-Low-Power Unitary Matrix Multiplier Based on Silicon Photonic MEMS

We propose and demonstrate an ultra-low-power 3×3 unitary matrix multiplier with MEMS-based tunable couplers and phase shifters. The static power consumption and tuning energy per tuning element are less than 0.13 µW and 115 pJ, respectively. © Optica Publishing Group 2022, © 2022 The Author(s

B7-Mediated Costimulation of CD4 T Cells Constrains Cytomegalovirus Persistence ▿

Cytomegalovirus (CMV) utilizes multiple strategies to modulate immunity and promote lifelong, persistent/latent infection, including suppressing T cell activation pathways. Here we examined the role of B7 costimulatory ligands in establishing immune détente from both the host and virus perspectives. Mice lacking both B7.1 and B7.2 showed reduced early expansion of CMV-specific CD4 T cells, consequently allowing for enhanced levels of persistent virus replication. In turn, a CMV mutant lacking expression of the m138 and m147.5 gene products, which restrict B7.1 and B7.2 expression in infected antigen-presenting cells, induced a more robust CD4 T cell response and showed decreased persistence. Together, these data reveal a requirement for B7-mediated signaling in regulating the CMV-specific CD4 T cell response and establishing host-virus equilibrium